Lead liver

Clinical Pharmacy Manager/Lead Liver Pharmacist Pharmacy Department, St Vincent s University Hospital Dublin, Ireland... 

Cortisone is a hormone produced by the cortex of the adrenal glands. As with other adrenal corticoid steroids, administration of cortisone leads to an increased deposition of liver glycogen. Tt can remove features of rheumatoid arthritis, but does not check the underlying disease it is used in various diseases of the eye, and is an antiallergic and anlifibroplastic agent. 

A large number of polycyclic aromatic hydrocarbons are known Many have been synthesized m the laboratory and several of the others are products of com bustion Benzo[a]pyrene for example is present m tobacco smoke contaminates food cooked on barbecue grills and collects m the soot of chimneys Benzo[a]pyrene is a carcinogen (a cancer causing substance) It is converted m the liver to an epoxy diol that can induce mutations leading to the uncontrolled growth of certain cells... 

Some commonly encountered materials arranged in order of decreasing p. are lead > BaSO > bone > muscle > blood > liver > fat > air. 

Xenobiotic induced disruption of female fertility follows essentially the same pattern as that of the male and can be caused by changes in pituitary-hypothalamic function, primary disruption of ovarian structure or hormone secretion, or changes in the rate of hormone deactivation. In addition, there may be changes in the synthesis of estrogen induced production of the yolk protein by the liver (vitellogenesis), which in turn can lead to failure to lay down sufficient yolk in the developing oocytes. Vitellogenesis provides a valuable biomarker for endocrine dysfunction in both sexes,but is more properly considered as part of the liver function. 

Solutions in contact with polyvinyl chloride can become contaminated with trace amounts of lead, titanium, tin, zinc, iron, magnesium or cadmium from additives used in the manufacture and moulding of PVC. V-Phenyl-2-naphthylamine is a contaminant of solvents and biological materials that have been in contact with black rubber or neoprene (in which it is used as an antioxidant). Although it was only an artefact of the separation procedure it has been isolated as an apparent component of vitamin K preparations, extracts of plant lipids, algae, livers, butter, eye tissue and kidney tissue [Brown Chem Br 3 524 1967]. 

The absorption, distribution, and accumulation of lead in the human body may be represented by a three-part model (6). The first part consists of red blood cells, which move the lead to the other two parts, soft tissue and bone. The blood cells and soft tissue, represented by the liver and kidney, constitute the mobile part of the lead body burden, which can fluctuate depending on the length of exposure to the pollutant. Lead accumulation over a long period of time occurs in the bones, which store up to 95% of the total body burden. However, the lead in soft tissue represents a potentially greater toxicological hazard and is the more important component of the lead body burden. Lead measured in the urine has been found to be a good index of the amount of mobile lead in the body. The majority of lead is eliminated from the body in the urine and feces, with smaller amounts removed by sweat, hair, and nails. 

Insulin is a peptide hormone, secreted by the pancreas, that regulates glucose metabolism in the body. Insufficient production of insulin or failure of insulin to stimulate target sites in liver, muscle, and adipose tissue leads to the serious metabolic disorder known as diabetes mellitus. Diabetes afflicts millions of people worldwide. Diabetic individuals typically exhibit high levels of glucose in the blood, but insulin injection therapy allows diabetic individuals to maintain normal levels of blood glucose. 

Cadmium is extremely toxic and accumulates in humans mainly in the kidneys and liver prolonged intake, even of very small amounts, leads to dysfunction of the kidneys. It acts by binding to the —SH group of cysteine residues in proteins and so inhibits SH enzymes. It can also inhibit the action of zinc enzymes by displacing the zinc. 

Ethanol metabolism occurs mainly in the liver and proceeds by oxidation in two steps, first to acetaldehyde (CHjCHO) and then to acetic add (CH3CO2H)- When continuously present in the body, ethanol and acetaldehyde are toxic, leading to the devastating physical and metabolic deterioration... 

Atovaquone, a hydroxynaphthoquinone, selectively inhibits the respiratory chain of protozoan mitochondria at the cytochrome bcl complex (complex III) by mimicking the natural substrate, ubiquinone. Inhibition of cytochrome bcl disrupts the mitochondrial electron transfer chain and leads to a breakdown of the mitochondrial membrane potential. Atovaquone is effective against all parasite stages in humans, including the liver stages. 

Following concurrent administration of two drugs, especially when they are metabolized by the same enzyme in the liver or small intestine, the metabolism of one or both drugs can be inhibited, which may lead to elevated plasma concentrations of the dtug(s), and increased pharmacological effects. The types of enzyme inhibition include reversible inhibition, such as competitive or non-competitive inhibition, and irreversible inhibition, such as mechanism-based inhibition. The clinically important examples of drug interactions involving the inhibition of metabolic enzymes are listed in Table 1 [1,4]. 

The co-administration of drugs which induce the metabolic enzymes in the liver or small intestine can reduce the plasma concentrations of drugs which are substrates of the enzyme, leading to reduced drug effects. For example, the plasma concentrations of many drugs which are substrates of the enzyme CYP3A4, such as cyclosporine, are decreased by coadministration of rifampicin, which is an inducer of CYP3A4. 

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